1. Field of the Invention
The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-(hydrogen or di(C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ine. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a 7-(hydrogen or di(C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ine in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a 7-(hydrogen or di(C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ine in a pharmaceutically acceptable carrier.
2. Description of the Prior Art
In W092/12717, Brem et al teach that some tetracyclines, particularly Minocycline, Chlortetracycline, Demeclocycline and Lymecycline are useful as inhibitors of angiogenesis. In Cancer Research 51, 672-675, Jan. 15, 1991, Brem et al teach that Minocycline inhibits angiogenesis to an extent comparable to that of the combination therapy of heparin and cortisone. In Cancer Research 52, 6702-6704, Dec, 1, 1992, Teicher et al teach that tumor growth is decreased and the number of metastases is reduced when the anti-angiogenic agent Minocycline is used in conjunction with cancer chemotherapy or radiation therapy.
It has now been found that certain 7-(hydrogen or di(C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ines are unexpectedly better inhibitors of endothelial and tumor cell proliferation than the tetracyclines, especially Minocycline, described by Brem et al and Teicher et al.